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Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells

Autophagy, an integral part of the waste recycling process, plays an important role in cellular physiology and pathophysiology. Impaired autophagic flux causes ectopic lipid deposition, which is defined as the accumulation of lipids in non-adipose tissue. Ectopic lipid accumulation is observed in pa...

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Autores principales: Kim, Hae-Suk, Ren, Guang, Kim, Teayoun, Bhatnagar, Sushant, Yang, Qinglin, Bahk, Young Yil, Kim, Jeong-a
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419289/
https://www.ncbi.nlm.nih.gov/pubmed/32782332
http://dx.doi.org/10.1038/s41598-020-70347-w
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author Kim, Hae-Suk
Ren, Guang
Kim, Teayoun
Bhatnagar, Sushant
Yang, Qinglin
Bahk, Young Yil
Kim, Jeong-a
author_facet Kim, Hae-Suk
Ren, Guang
Kim, Teayoun
Bhatnagar, Sushant
Yang, Qinglin
Bahk, Young Yil
Kim, Jeong-a
author_sort Kim, Hae-Suk
collection PubMed
description Autophagy, an integral part of the waste recycling process, plays an important role in cellular physiology and pathophysiology. Impaired autophagic flux causes ectopic lipid deposition, which is defined as the accumulation of lipids in non-adipose tissue. Ectopic lipid accumulation is observed in patients with cardiometabolic syndrome, including obesity, diabetes, insulin resistance, and cardiovascular complications. Metformin is the first line of treatment for type 2 diabetes, and one of the underlying mechanisms for the anti-diabetic effect of metformin is mediated by the stimulation of AMP-activated protein kinase (AMPK). Because the activation of AMPK is crucial for the initiation of autophagy, we hypothesize that metformin reduces the accumulation of lipid droplets by increasing autophagic flux in vascular endothelial cells. Incubation of vascular endothelial cells with saturated fatty acid (SFA) increased the accumulation of lipid droplets and impaired autophagic flux. We observed that the accumulation of lipid droplets was reduced, and the autophagic flux was enhanced by treatment with metformin. The knock-down of AMPKα by using siRNA blunted the effect of metformin. Furthermore, treatment with SFA or inhibition of autophagy increased leukocyte adhesion, whereas treatment with metformin decreased the SFA-induced leukocyte adhesion. The results suggest a novel mechanism by which metformin protects vascular endothelium from SFA-induced ectopic lipid accumulation and pro-inflammatory responses. In conclusion, improving autophagic flux may be a therapeutic strategy to protect endothelial function from dyslipidemia and diabetic complications.
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spelling pubmed-74192892020-08-13 Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells Kim, Hae-Suk Ren, Guang Kim, Teayoun Bhatnagar, Sushant Yang, Qinglin Bahk, Young Yil Kim, Jeong-a Sci Rep Article Autophagy, an integral part of the waste recycling process, plays an important role in cellular physiology and pathophysiology. Impaired autophagic flux causes ectopic lipid deposition, which is defined as the accumulation of lipids in non-adipose tissue. Ectopic lipid accumulation is observed in patients with cardiometabolic syndrome, including obesity, diabetes, insulin resistance, and cardiovascular complications. Metformin is the first line of treatment for type 2 diabetes, and one of the underlying mechanisms for the anti-diabetic effect of metformin is mediated by the stimulation of AMP-activated protein kinase (AMPK). Because the activation of AMPK is crucial for the initiation of autophagy, we hypothesize that metformin reduces the accumulation of lipid droplets by increasing autophagic flux in vascular endothelial cells. Incubation of vascular endothelial cells with saturated fatty acid (SFA) increased the accumulation of lipid droplets and impaired autophagic flux. We observed that the accumulation of lipid droplets was reduced, and the autophagic flux was enhanced by treatment with metformin. The knock-down of AMPKα by using siRNA blunted the effect of metformin. Furthermore, treatment with SFA or inhibition of autophagy increased leukocyte adhesion, whereas treatment with metformin decreased the SFA-induced leukocyte adhesion. The results suggest a novel mechanism by which metformin protects vascular endothelium from SFA-induced ectopic lipid accumulation and pro-inflammatory responses. In conclusion, improving autophagic flux may be a therapeutic strategy to protect endothelial function from dyslipidemia and diabetic complications. Nature Publishing Group UK 2020-08-11 /pmc/articles/PMC7419289/ /pubmed/32782332 http://dx.doi.org/10.1038/s41598-020-70347-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Hae-Suk
Ren, Guang
Kim, Teayoun
Bhatnagar, Sushant
Yang, Qinglin
Bahk, Young Yil
Kim, Jeong-a
Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells
title Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells
title_full Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells
title_fullStr Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells
title_full_unstemmed Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells
title_short Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells
title_sort metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419289/
https://www.ncbi.nlm.nih.gov/pubmed/32782332
http://dx.doi.org/10.1038/s41598-020-70347-w
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